Oxygen is a vital component of biological energy metabolism and plays a central role in many cellular processes. In solid tumors, oxygen distributions are highly heterogeneous and are, in general, at much lower levels of oxygen than normal tissues. At these low concentrations of oxygen, cancer cells can resist both radiotherapy and chemotherapeutics. Real-time continuous monitoring of local oxygen content at the cellular level is important for understanding the biophysical properties of migration and sensitivity to chemotherapeutics as related to the surrounding oxygen content.
Conventional Clark electrodes are currently being used for oxygen sensing (Clark, L. C. et al., Transactions American Society for Artificial Internal Organs 2 (1956) 41-48). However, these sensors consume oxygen during measurements, are invasive, and are difficult to miniaturize to provide localized oxygen information. Such sensors are also limited to single-point measurements and cannot reveal either 2D or 3D oxygen distributions in heterogeneous systems. Recently, optical sensors based on luminescence quenching of oxygen sensitive probes (typically organometallic complexes and metallo porphyrins) have attracted a great deal of attention (Wang, X. et al., Trends Anal. Chem. 29 (2010) 319-338). These molecular probes are usually doped within protective polymer matrix materials, commonly in the forms of films, that serve as a solvent for the luminescent molecules, provide mechanical support, help improve selectivity by preventing penetration of interfering specie, as well as adjust the quenching behavior of the sensor by tailoring the probe-matrix interactions (Florescu, M., et al., Sens. Actuators, B, 97 (2004) 39-44). These probes however, are usually not very compatible with standard cell culture devices and in general have longer response times due to a 2D configuration that limits the surface area susceptible to rapid oxygen diffusion. Biological applications further require that these sensors function in an environment in which oxygen concentrations vary over a relatively small range. Therefore, high sensitivities are considered desirable.
There is a need for oxygen sensors that are sensitive, non-invasive, more easily miniaturized, can be integrated with cell culture devices, lack of oxygen consumption, and freedom from electrical interference.